This invention is generally in the field of tissue engineering, and more particularly pertains to synthetic scaffold materials and methods useful in directing tissue growth in vivo or ex vivo.
Severe traumatic injury or invasive surgical procedures on a peripheral nerve can result in a gap between two nerve stumps. The clinical “gold standard” for bridging peripheral nerve gaps is the use of autografts, typically, the sensory sural nerve. However, the use of autografts is limited by the inadequate availability of nerves to use in the autograft (IJkema-Paassen, et al., Biomaterials 25:1583-92 (2004)), the lack of co-adaptation between the injured nerve and the nerve graft due to size/length/modality mismatch (Nichols, et al., Exp. Neurol. 190:347-55 (2004)), and functional loss at the donor sites (Bini, et al., J. Biomed. Mater. Res A 68:286-95 (2004)). Moreover, complications at the donor site such as numbness, hyperesthesia, or formation of painful neuroma also have to be addressed (Itoh, et al., Biomaterials 23:4475-81 (2002); Matsuyama, et al., Neurol. Med. Chir. (Tokyo) 40:187-99 (2000)). Therefore, it is imperative that alternative approaches that are ready-to-use, pre-customized for reducing the mismatch, and suitable for both sensory and motor nerve regeneration are developed.
Many research and development efforts are focused on manipulating cell growth, proliferation, and differentiation to repair or replace damaged tissue structures in the body, or to grow tissues and organs. One approach is the use of engineered tissue scaffolds.
Tubular nerve conduits have been used clinically for repairing peripheral nerve injury (Taras, et al., J. Hand Ther. 18:191-97 (2005)). These nerve conduits, which are made of non-porous silicone or porous natural/synthetic polymers, bridge the injured nerve stumps and help form a fibrin cable which provides a substrate for the ingrowth of Schwann cells and other cells such as fibroblasts. The infiltrating Schwann cells reorganize to create longitudinally oriented bands of Bungner, which serve as a guiding substrate and a source of neurotrophic factors to foster axonal regrowth (Bungner, 1891; Ide, Neurosci Res. 25:101-21 (1996)). However, these approaches are limited in their ability to enable regeneration across long nerve gaps, and have been unsuccessful in promoting regeneration across gaps longer than 15 mm in rodents. Failure of nerve regeneration across long gaps, i.e., those greater than 15 mm, seems to be the result of a lack of the formation of an initial fibrin cable, which is necessary for the formation of the bands of Bungner (Lundborg, et al., Exp. Neuro. 76:361-75 (1982)).
Conventional tissue engineering scaffolds are isotropic and provide no directional cues to promote directional cell and tissue growth and regeneration, and require the addition of exogenously delivered neurotrophic factors to increase the intrinsic growth capacity of injured axons. Accordingly, there exists a need to develop a scaffold that promotes directional cell and tissue growth and regeneration across long nerve gaps. More generally, there exists a need to develop an engineered scaffold that promotes directional cell and tissue growth and regeneration for use in a variety of applications, such as cartilage, bone, neural, and cardiovascular tissue engineering.